Dosing regimens for n-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-YL)-2-(4-sulfamoylphenyl)acetamide for use in treating or preventing a dengue virus disease or disorder

Abstract

Disclosed herein are dosage and dosage regimens for N-(3-cyano-5-(cyclohexylmethyl)-6,6- dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for the treatment or prevention of a dengue virus disease or disorder. In addition, the invention provides using such dosage and dosage regimens in methods for the treatment or prevention of a dengue virus disease or disorder: Compound (1).

Description

[0001] DOSING REGIMENS FOR N-(3-CYANO-5-(CYCLOHEXYLMETHYL)-6,6-DIMETHYL-4, 5,6,7- TETRAHYDROTHIENO[3,2-C]PYRIDIN-2-YL)-2-(4-SULFAMOYLPHENYL)ACETAMIDE FOR USE IN TREATING OR PREVENTING A DENGUE VIRUS DISEASE OR DISORDER

[0002] CROSS-REFERENCES TO RELATED APPLICATIONS

[0003] This application claims the benefit of US Provisional Patent Application No. 63 / 647,395 filed May 14, 2024, which is incorporated by reference herein in its entirety and for all purposes.

[0004] FIELD OF THE INVENTION

[0005] This invention relates to dose and dosing regimens for N-(3-cyano-5-(cyclohexylmethyl)-6,6- dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide, or a pharmaceutically acceptable salt thereof, for the treatment or prevention of a dengue virus disease or disorder.

[0006] BACKGROUND OF THE INVENTION

[0007] Dengue virus is a mosquito-borne flavivirus endemic in over 100 countries that infects an estimated 390 million people per year (Bhatt S, Gething PW, Brady OJ, et al (2013) The global distribution and burden of dengue. Nature; 496). The virus is divided into four closely related but distinct serotypes (DENV-1 , DENV-2, DENV-3, and DENV-4), all of which can cause disease. Symptomatic cases can range from the flu-like dengue fever to more severe and life-threatening forms such as dengue shock syndrome or dengue hemorrhagic fever. Fueled by urbanization and globalization (Gubler DJ (2011) Dengue, Urbanization and Globalization: The Unholy Trinity of the 21st Century. Trop Med Health; 39:3-11), the incidence of dengue has increased 30-fold over the past 50 years (WHO 2012), with severe outbreaks exerting a huge burden on populations, health systems, and economies (Shepard DS, Undurraga EA, Halasa YA, et al (2016) The global economic burden of dengue: a systematic analysis. Lancet Infect Dis; 16:935-41 ; Stanaway JD, Shepard DS, Undurraga EA, et al (2016) The global burden of dengue: an analysis from the Global Burden of Disease Study 2013. Lancet Infect Dis; 16, 712- 23). Effective control of dengue should include a combination of preventative strategies such as vector control and vaccines, along with improved clinical care such as the use of antivirals. Preventative measures such as vector control strategies show promise, however, for many reasons they are difficult to be successfully implemented and have not yet shown long-term efficacy in containing recent epidemics or averting the global spread of dengue (Reiner RC, Achee N, Barrera RT, et al (2016) Quantifying the Epidemiological Impact of Vector Control on Dengue. PLoS Negl Trop Dis; 10). Dengvaxia® (Dengvaxia USPI 2023), was approved for use only in individuals who have had a prior dengue infection (WHO 2018), severely limiting its usage. The other vaccine QDENGA®, was approved in Indonesia and Europe for prevention of dengue disease in individuals 6 to 45 years of age, however, it did not demonstrate efficacy against virologically confirmed dengue caused by serotype DENV-3 and there were not enough cases by serotype DENV-4 to draw conclusion. In terms of clinical care, there is currently no specific treatment for dengue infection - standard of care includes monitoring of patients and replacement of fluids when necessary. A dengue antiviral could help reduce the morbidity and mortality associated with infection; however, none currently exists.

[0008] SUMMARY OF THE INVENTION

[0009] There remains a need for treatment or preventing a dengue virus disease or disorder. International patent application WO2019244047A1 discloses N-substitued tetrahydrothienopyridine derivatives and their use in treating a disease caused by a viral infection, in particular a disease caused by dengue virus infections. However, there is no disclosure regarding a human dose or dosing regimen. Accordingly, the invention provided herein describes dosages, dosage forms, medicaments, compositions and dosing regimens for N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound 1), or a pharmaceutically acceptable salt thereof, Compound (1).

[0010] In addition the invention provided herein describes the use of such dosages, dosage forms, medicaments, compositions and dosing regimens for the treatment or prevention of a dengue virus disease or disorder.

[0011] One aspect of the invention is a method for treating or preventing a dengue virus disease or disorder in a subject in need thereof, comprising orally administering a therapeutically effective amount of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin- 2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, to the subject, wherein Compound (1), or a pharmaceutically acceptable salt thereof, is orally administered once a day.

[0012] One aspect of the invention is a method for treating or preventing a dengue virus disease or disorder in a subject in need thereof, comprising orally administering a therapeutically effective amount of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin- 2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, to the subject, wherein Compound (1), or a pharmaceutically acceptable salt thereof, is orally administered once a day at a dose of about 10 mg to about 400 mg.

[0013] Another aspect of the invention is a method for treating or preventing a dengue virus disease or disorder in a subject in need thereof, comprising orally administering a therapeutically effective amount of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, to the subject, wherein Compound (1), or a pharmaceutically acceptable salt thereof, is orally administered twice a day.

[0014] Another aspect of the invention is a method for treating or preventing a dengue virus disease or disorder in a subject in need thereof, comprising orally administering a therapeutically effective amount of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, to the subject, wherein Compound (1), or a pharmaceutically acceptable salt thereof, is orally administered twice a day where each dose is about 300 mg to about 500 mg.

[0015] Another aspect of the invention is a method for treating or preventing a dengue virus disease or disorder in a subject in need thereof, comprising orally administering a therapeutically effective amount of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, to the subject, wherein Compound (1), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 5 days where each dose is about 300 mg to about 500 mg. In certain embodiments, N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyljacetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day where each dose is about 300 mg, about 400 mg or about 500 mg. In certain embodiments, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day where each dose is about 500 mg. In certain embodiments, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day where each dose is 500 mg.

[0016] In certain embodiments of the above methods of treatment the N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyljacetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered as a N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide mesylate salt.

[0017] In certain embodiments of the above methods of treatment the N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyljacetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered as a N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide gentisate salt. In certain embodiments of the above methods of treatment the N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered as a N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide free base.

[0018] Another aspect of the invention is N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, wherein Compound (1), or a pharmaceutically acceptable salt thereof, is orally administered once a day.

[0019] Another aspect of the invention is N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, wherein Compound (1), or a pharmaceutically acceptable salt thereof, is orally administered once a day at a dose of about 10 mg to about 400 mg.

[0020] Another aspect of the invention is N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, wherein Compound (1), or a pharmaceutically acceptable salt thereof, is orally administered twice a day.

[0021] Another aspect of the invention is N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, wherein Compound (1), or a pharmaceutically acceptable salt thereof, is orally administered twice a day where each dose is about 300 mg to about 500 mg.

[0022] Another aspect of the invention is N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, wherein Compound (1), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 5 days where each dose is about 300 mg to about 500 mg. In certain embodiments of this aspect, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day where each dose is about 300 mg, about 400 mg or about 500 mg. In certain embodiments of this aspect, N-(3- cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day where each dose is about 500 mg. In certain embodiments of this aspect, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day where each dose is 500 mg.

[0023] In certain embodiments of the above use in the treatment or prevention of a dengue virus disease or disorder, the N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered as a N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide mesylate salt.

[0024] In certain embodiments of the above use in the treatment or prevention of a dengue virus disease or disorder, the N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered as a N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide gentisate salt.

[0025] In certain embodiments of the above use in the treatment or prevention of a dengue virus disease or disorder, the N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered as a N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide free base.

[0026] Another aspect of the invention is the use of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-

[0027] 4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the treatment or prevention of a dengue virus disease or disorder, wherein Compound (1), or a pharmaceutically acceptable salt thereof, is orally administered once a day.

[0028] Another aspect of the invention is the use of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-

[0029] 4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the treatment or prevention of a dengue virus disease or disorder, wherein Compound (1), or a pharmaceutically acceptable salt thereof, is orally administered once a day at a dose of about 10 mg to about 400 mg.

[0030] Another aspect of the invention is the use of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-

[0031] 4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the treatment or prevention of a dengue virus disease or disorder, wherein Compound (1), or a pharmaceutically acceptable salt thereof, is orally administered twice a day.

[0032] Another aspect of the invention is the use of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-

[0033] 4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the treatment or prevention of a dengue virus disease or disorder, wherein Compound (1), or a pharmaceutically acceptable salt thereof, is orally administered twice a day where each dose is about 300 mg to about 500 mg.

[0034] Another aspect of the invention is the use of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-

[0035] 4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the treatment or prevention of a dengue virus disease or disorder, wherein Compound (1), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 5 days where each dose is about 300 mg to about 500 mg. In certain embodiments of this aspect, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day where each dose is about 300 mg, about 400 mg or about 500 mg. In certain embodiments of this aspect, N-(3- cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day where each dose is about 500 mg. In certain embodiments of this aspect, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day where each dose is 500 mg.

[0036] In certain embodiments of the above use of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-

[0037] 4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, the N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-

[0038] 4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered as a N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide mesylate salt.

[0039] In certain embodiments of the above use of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-

[0040] 4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, the N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-

[0041] 4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered as a N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide gentisate salt.

[0042] In certain embodiments of the above use of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-

[0043] 4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, the N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-

[0044] 4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered as a N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide free base. Another aspect of the invention is a medicament comprising N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, wherein Compound (1), or a pharmaceutically acceptable salt thereof, is present in an amount of about 10 mg to about 400 mg.

[0045] Another aspect of of the invention is a medicament comprising N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, wherein Compound (1), or a pharmaceutically acceptable salt thereof, is present in an amount of about 50 mg to about 500 mg.

[0046] In certain embodiments of the above medicament aspects the N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is present as a N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide mesylate salt.

[0047] In certain embodiments of the above medicament aspects the N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is present as a N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide gentisate salt.

[0048] In certain embodiments of the above medicament aspects the N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is present as a N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide free base.

[0049] One aspect of the invention is a dosing regimen for treating or preventing a dengue virus disease or disorder, wherein the regimen comprises orally administering N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, once a day.

[0050] One aspect of the invention is a dosing regimen for treating or preventing a dengue virus disease or disorder, wherein the regimen comprises orally administering N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, once a day at a dose of about 10 mg to about 400 mg.

[0051] Another aspect of the invention is a dosing regimen for treating or preventing a dengue virus disease or disorder, wherein the regimen comprises orally administering N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, twice a day.

[0052] Another aspect of the invention is a dosing regimen for treating or preventing a dengue virus disease or disorder, wherein the regimen comprises orally administering N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, twice a day where each dose is about 300 mg to about 500 mg.

[0053] Another aspect of the invention is a dosing regimen for treating or preventing a dengue virus disease or disorder, wherein the regimen comprises orally administering N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, twice a day for 5 days where each dose is about 300 mg to about 500 mg.

[0054] In certain embodiments of the above dosage regimens the N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered as a N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide mesylate salt.

[0055] In certain embodiments of the above dosage regimens the N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered as a N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide gentisate salt.

[0056] In certain embodiments of the above dosage regimens the N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered as a N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide free base.

[0057] In certain embodiments of the above aspects the dengue virus disease or disorder is dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). In other embodiments of the above aspects the dengue virus disease or disorder is dengue hemorrhagic fever (DHF).

[0058] DETAILED DESCRIPTION OF THE INVENTION

[0059] Definitions

[0060] The terms “composition” or “pharmaceutical composition,” as used herein, refers to a mixture of Compound (1), or pharmaceutically acceptable salt thereof, and one or more one or more pharmaceutically acceptable carriers, in a form suitable for oral or parenteral administration.

[0061] The terms “carrier(s)” or "pharmaceutically acceptable carrier(s)", as used herein, includes any and all solvents, dispersion media, coatings, surfactants, antioxidants, preservatives (e.g., antibacterial agents, antifungal agents), isotonic agents, absorption delaying agents, salts, preservatives, drugs, drug stabilizers, binders, excipients, disintegration agents, lubricants, sweetening agents, flavoring agents, dyes, and the like and combinations thereof, as would be known to those skilled in the art (see, for example, Remington's Pharmaceutical Sciences, 18th Ed. Mack Printing Company, 1990, pp. 1289-1329). Except insofar as any conventional carrier is incompatible with the active ingredient, its use in the therapeutic or pharmaceutical compositions is contemplated.

[0062] The phrase “pharmaceutically acceptable”, as used herein, means a nontoxic material that does not interfere with the effectiveness of the biological activity of the active ingredient(s).

[0063] The term “patient” or “subject” as used herein, encompasses mammals and non-mammals. Examples of mammals include, but are not limited to, humans, chimpanzees, apes, monkeys, cattle, horses, sheep, goats, swine; rabbits, dogs, cats, rats, mice, guinea pigs, and the like. Examples of non-mammals include, but are not limited to, birds, fish and the like. Frequently the patient or subject is a human.

[0064] The terms “a patient in need” or “subject in need”, refers to a patient or subject, which would benefit biologically, medically or in quality of life from treatment with Compound (1), or a pharmaceutically acceptable salt thereof.

[0065] The term "therapeutically effective amount", as used herein, refers to an amount of the Compound (1), or a pharmaceutically acceptable salt thereof, which is sufficient to achieve the stated effect. Accordingly, a therapeutically effective amount of Compound (1), used for the treatment or prevention of a dengue virus disease or disorder will be an amount sufficient to treat or prevent a dengue virus disease or disorder.

[0066] The term “treat”, “treating”, “treatment” or “therapy” as used herein comprises a treatment relieving, reducing or alleviating at least one symptom in a patient, or effecting a delay of progression of a dengue virus disease or disorder in a patient. For example, treatment can be the diminishment of one or several symptoms of a disorder or complete eradication of a disorder.

[0067] The terms “prevent”, “preventing” or “prevention”, as used herein, denotes arresting, delaying the onset (i.e. , the period prior to clinical manifestation of a disease) and / or reducing the risk of developing or worsening of a dengue virus disease or disorder.

[0068] The term “dosing regimen”, as used herein, refers to the pattern of dosing used during the treatment or prevention of a disease or disorder and is also referred to as a "dosing schedule".

[0069] The term “about”, “approximately”, or “approximate”, when used in connection with a numerical value provided herein, means that a collection or range of values is included. For example, “about X mg” encompasses the numeric value X and a range of values from ±0.0001% to ± 20% of the value of X. By way of example, “about 500 mg” means 500 mg and includes 500 mg ±0.0005 mg to ± 100 mg.

[0070] In certain embodiments, the term “about”, “approximately”, or “approximate”, means the numeric value X and a range of values from ±0.0001 % to ± 15% of the value of X. By way of example, “about 500 mg” means 500 mg and includes 500 mg ±0.0005 mg to ± 75 mg.

[0071] In certain embodiments, the term “about”, “approximately”, or “approximate”, means the numeric value X and a range of values from ±0.0001% to ± 10% of the value of X. By way of example, “about 500 mg” means 500 mg and includes 500 mg ±0.0005 mg to ± 50 mg.

[0072] In certain embodiments, the term “about”, “approximately”, or “approximate”, means the numeric value X and a range of values from ±0.0001 % to ± 5% of the value of X. By way of example, “about 500 mg” means 500 mg and includes 500 mg ±0.0005 mg to ± 25 mg.

[0073] In certain embodiments, the term “about”, “approximately”, or “approximate”, means the numeric value X and a range of values from ±0.0001 % to ± 4% of the value of X. By way of example, “about 500 mg” means 500 mg and includes 500 mg ±0.0005 mg to ± 20 mg.

[0074] In certain embodiments, the term “about”, “approximately”, or “approximate”, means the numeric value X and a range of values from ±0.0001 % to ± 3% of the value of X. By way of example, “about 500 mg” means 500 mg and includes 500 mg ±0.0005 mg to ± 15 mg.

[0075] In certain embodiments, the term “about”, “approximately”, or “approximate”, means the numeric value X and a range of values from ±0.0001 % to ± 2% of the value of X. By way of example, “about 500 mg” means 500 mg and includes 500 mg ±0.0005 mg to ± 10 mg.

[0076] In certain embodiments, the term “about”, “approximately”, or “approximate”, means the numeric value X and a range of values from ±0.0001 % to ± 1 % of the value of X. By way of example, “about 500 mg” means 500 mg and includes 500 mg ±0.0005 mg to ± 5 mg.

[0077] In certain embodiments, the term “about”, “approximately”, or “approximate”, means the numeric value X and a range of values from ±0.0001% to ± 0.75% of the value of X. By way of example, “about 500 mg” means 500 mg and includes 500 mg ±0.0005 mg to ± 3.75 mg.

[0078] In certain embodiments, the term “about”, “approximately”, or “approximate”, means the numeric value X and a range of values from ±0.0001 % to ± 0.5% of the value of X. By way of example, “about 500 mg” means 500 mg and includes 500 mg ±0.0005 mg to ± 2.5 mg.

[0079] In certain embodiments, the term “about”, “approximately”, or “approximate”, means the numeric value X and a range of values from ±0.0001% to ± 0.25% of the value of X. By way of example, “about 500 mg” means 500 mg and includes 500 mg ±0.0005 mg to ± 1.25 mg.

[0080] In certain embodiments, the term “about”, “approximately”, or “approximate”, means the numeric value X and a range of values from ±0.0001 % to ± 0.2% of the value of X. By way of example, “about 500 mg” means 500 mg and includes 500 mg ±0.0005 mg to ± 1mg.

[0081] In certain embodiments, the term “about”, “approximately”, or “approximate”, means the numeric value X and a range of values from ±0.0001 % to ± 0.1 % of the value of X. By way of example, “about 500 mg” means 500 mg and includes 500 mg ±0.0005 mg to ± 0.5 mg.

[0082] In one embodiment, the term “about” refers to a range of values which are 10% more or less than the specified value. In another embodiment, the term “about” refers to a range of values which are 5% more or less than the specified value. In another embodiment, the term “about” refers to a range of values which are 1% more or less than the specified value.

[0083] Recitation of ranges of values are merely intended to serve as a shorthand method of referring individually to each separate value falling within the range, unless otherwise indicated herein, and each separate value is incorporated into the specification as if it were individually recited herein. A range used herein, unless otherwise specified, includes the two limits of the range. For example, the terms “between X and Y” and “range from X to Y, are inclusive of X and Y and the integers there between. On the other hand, when a series of individual values are referred to in the disclosure, any range including any of the two individual values as the two end points is also conceived in this disclosure. For example, the expression "a dose of about 10 mg, about 30 mg, about 50 mg, about 100 mg, about 150 mg, about 300 mg, or about 400 mg", also means “a dose ranging from 10 to 400 mg”. Similarly, the expression “each dose is about 300 mg, about 400 mg or about 500 mg” means “each dose is in a dose ranging from 300 to 500 mg”.

[0084] The term “N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide mesylate salt”, as used herein refers to the mesylate salt of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)) and has the following structure:

[0085] The term “N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide gentisate salt”, as used herein refers to the gentisate salt of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)) and has the following structure:

[0086] The term “N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide free base”, as used herein refers to the neutral (i.e. uncharged) form of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)) and has the following structure: Compound (1).

[0087] Description of Embodiments of the Invention

[0088] The invention provides dosage and dosing regimens for N-(3-cyano-5-(cyclohexylmethyl)- 6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof: Compound (1).

[0089] In an embodiment, the invention provides dosage and dosing regimens for N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide free base, while in another embodiment, the invention provides dosage and dosing regimens for N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide mesylate salt, while in a further embodiment the invention provides dosage and dosing regimens for N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide gentisate salt.

[0090] Such dosing regimens (i.e dosing schedules) for the administration of Compound (1), or a pharmaceutically acceptable salt thereof, is the daily administration of Compound (1), or a pharmaceutically acceptable salt thereof, wherein Compound (1), or a pharmaceutically acceptable salt thereof, is orally administered once a day, or Compound (1), or a pharmaceutically acceptable salt thereof, is orally administered twice a day.

[0091] Specifically, such dosing regimens (i.e dosing schedules) for the administration of N-(3- cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1), as a free base, mesylate salt or gentisate salt thereof, is the daily administration of Compound (1), or a pharmaceutically acceptable salt thereof, wherein Compound (1), or a pharmaceutically acceptable salt thereof, is orally administered once a day, or Compound (1), or a pharmaceutically acceptable salt thereof, is orally administered twice a day.

[0092] The following description of the dosing regimens for Compound (1), or a pharmaceutically acceptable salt thereof, are also applicable for the administration of N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1), as a free base, mesylate salt or gentisate salt thereof.

[0093] Such dosing regimens are continuous dosing schedules, wherein Compound (1), or a pharmaceutically acceptable salt thereof, is orally administered once a day during a dosing period, or Compound (1), or a pharmaceutically acceptable salt thereof, is orally administered twice a day during a dosing period.

[0094] A dosing period is the number of days recommended for dosing of Compound (1), or a pharmaceutically acceptable salt thereof. For example, a dosing period can be 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days. In an embodiment the dosing period is 1 day. In an embodiment the dosing period is 2 days. In an embodiment the dosing period is 3 days. In an embodiment the dosing period is 4 days. In an embodiment the dosing period is 5 days. In an embodiment the dosing period is 6 days. In an embodiment the dosing period is 7 days. In a preferred embodiment, the dosing period is 5 days.

[0095] Accordingly, certain aspects and examples of dosage and dosing regimens of the invention are provided in the following embodiments.

[0096] Provided herein is a dosing regimen for treating or preventing a dengue virus disease or disorder, wherein the regimen comprises orally administering N-(3-cyano-5-(cyclohexylmethyl)- 6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, once a day, or the regimen comprises orally administering N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1), or a pharmaceutically acceptable salt thereof, twice a day.

[0097] In an embodiment of such dosing regimens, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl- 4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day at a dose of about 10 mg to about 400 mg, or N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1), or a pharmaceutically acceptable salt thereof), is orally administered twice a day where each dose is about 300 mg to about 500 mg.

[0098] In an aspect of the dosing regimens for treating or preventing a dengue virus disease or disorder, the regimen comprises orally administering N-(3-cyano-5-(cyclohexylmethyl)-6,6- dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, once a day.

[0099] In a certain embodiment of such once a day dosing regimens, N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day at a dose of about 10 mg to about 400 mg.

[0100] In a certain embodiment of such once a day dosing regimens, N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day at a dose of about 10 mg, about 30 mg, about 50 mg, about 100 mg, about 150 mg, about 300 mg, or about 400 mg.

[0101] In a certain embodiment of such once a day dosing regimens, N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day at a dose of about 300 mg, or about 400 mg.

[0102] In a certain embodiment of such once a day dosing regimens, N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day at a dose of about 400 mg.

[0103] In a certain embodiment of such once a day dosing regimens, N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day at a dose of 400 mg.

[0104] In an embodiment of such once a day dosing regimens, N-(3-cyano-5-(cyclohexylmethyl)- 6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days.

[0105] In an embodiment of such once a day dosing regimens, N-(3-cyano-5-(cyclohexylmethyl)- 6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day for 5 days.

[0106] In a certain embodiment of such once a day dosing regimens, N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days at a dose of about 10 mg to about 400 mg.

[0107] In a certain embodiment of such once a day dosing regimens, N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day for 5 days at a dose of about 10 mg to about 400 mg.

[0108] In a certain embodiment of such once a day dosing regimens, N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days at a dose of about 10 mg, about 30 mg, about 50 mg, about 100 mg, about 150 mg, about 300 mg, or about 400 mg.

[0109] In a certain embodiment of such once a day dosing regimens, N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day for 5 days at a dose of about 10 mg, about 30 mg, about 50 mg, about 100 mg, about 150 mg, about 300 mg, or about 400 mg.

[0110] In a certain embodiment of such once a day dosing regimens, N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days at a dose of about 300 mg, or about 400 mg.

[0111] In a certain embodiment of such once a day dosing regimens, N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day for 5 days at a dose of about 300 mg, or about 400 mg.

[0112] In a certain embodiment of such once a day dosing regimens, N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days at a dose of about 400 mg.

[0113] In a certain embodiment of such once a day dosing regimens, N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day for 5 days at a dose of about 400 mg.

[0114] In a certain embodiment of such once a day dosing regimens, N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days at a dose of 400 mg.

[0115] In a certain embodiment of such once a day dosing regimens, N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day for 5 days at a dose of 400 mg.

[0116] In another aspect of the dosing regimen for treating or preventing a dengue virus disease or disorder, the regimen comprises orally administering N-(3-cyano-5-(cyclohexylmethyl)-6,6- dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, twice a day.

[0117] In a certain embodiment of such twice a day dosing regimens, N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day where each dose is about 300 mg to about 500 mg.

[0118] In a certain embodiment of such twice a day dosing regimens, N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day where each dose is about 300 mg, about 400 mg or about 500 mg.

[0119] In a certain embodiment of such twice a day dosing regimens, N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day where each dose is about 400 mg or about 500 mg.

[0120] In a certain embodiment of such twice a day dosing regimens, N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day where each dose is about 400 mg.

[0121] In a certain embodiment of such twice a day dosing regimens, N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day where each dose is about 500 mg.

[0122] In a certain embodiment of such twice a day dosing regimens, N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day where each dose is 500 mg.

[0123] In an embodiment of such twice a day dosing regimens, N-(3-cyano-5-(cyclohexylmethyl)- 6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days.

[0124] In an embodiment of such twice a day dosing regimens, N-(3-cyano-5-(cyclohexylmethyl)- 6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 5 days.

[0125] In a certain embodiment of such twice a day dosing regimens, N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days where each dose is about 300 mg to about 500 mg.

[0126] In a certain embodiment of such twice a day dosing regimens, N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 5 days where each dose is about 300 mg to about 500 mg.

[0127] In a certain embodiment of such twice a day dosing regimens, N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days where each dose is about 300 mg, about 400 mg, or about 500 mg.

[0128] In a certain embodiment of such twice a day dosing regimens, N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 5 days where each dose is about 300 mg, about 400 mg, or about 500 mg.

[0129] In a certain embodiment of such twice a day dosing regimens, N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days where each dose is about 400 mg, or about 500 mg.

[0130] In a certain embodiment of such twice a day dosing regimens, N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 5 days where each dose is about 400 mg, or about 500 mg.

[0131] In a certain embodiment of such twice a day dosing regimens, N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days where each dose is about 400 mg.

[0132] In a certain embodiment of such twice a day dosing regimens, N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 5 days where each dose is about 400 mg.

[0133] In a certain embodiment of such twice a day dosing regimens, N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days where each dose is about 500 mg. In a certain embodiment of such twice a day dosing regimens, N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 5 days where each dose is about 500 mg.

[0134] In a certain embodiment of such twice a day dosing regimens, N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days where each dose is 500 mg.

[0135] In a certain embodiment of such twice a day dosing regimens, N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 5 days where each dose is 500 mg.

[0136] In certain embodiments of the above dosage regimens the N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered as a N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide mesylate salt.

[0137] In certain embodiments of the above dosage regimens the N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered as a N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide gentisate salt.

[0138] In certain embodiments of the above dosage regimens the N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered as a N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide free base.

[0139] In certain embodiments of the above dosage regimens the dengue virus disease or disorder is dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). In other embodiments of the above aspects the dengue virus disease or disorder is dengue hemorrhagic fever (DHF).

[0140] Pharmaceutical Compositions, Medicaments and Dosage Forms

[0141] In another aspect, the present invention provides a pharmaceutical composition comprising N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers.

[0142] Typically, the pharmaceutical compositions comprising N-(3-cyano-5-(cyclohexylmethyl)- 6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide, or a pharmaceutically acceptable salt thereof, further comprise one or more of: a) diluents, e.g., lactose, dextrose, sucrose, mannitol, sorbitol, cellulose and / or glycine; b) lubricants, e.g., silica, talcum, stearic acid, its magnesium or calcium salt and / or polyethyleneglycol; c) binders, e.g., magnesium aluminum silicate, starch paste, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose and / or polyvinylpyrrolidone; if desired d) disintegrants, e.g., starches, agar, alginic acid or its sodium salt, or effervescent mixtures; and e) absorbents, colorants, flavors and sweeteners.

[0143] In a certain embodiment the pharmaceutical composition comprising N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide, or a pharmaceutically acceptable salt thereof, also comprises mannitol, microcrystalline cellulose, croscarmellose sodium, hydroxypropyl cellulose, colloidal silicon dioxide and magnesium stearate.

[0144] Such pharmaceutical compositions can be formulated for oral administration and can be administered as a pharmaceutical dosage form such as capsules, tablets, pills, granules or powders. In certain embodiments tablets may be either film coated or enteric coated according to methods known in the art.

[0145] Accordingly, the present invention also provides a pharmaceutical unit dosage form, wherein the pharmaceutical unit dosage form is a capsule comprising N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers selected from: a) diluents, e.g., lactose, dextrose, sucrose, mannitol, sorbitol, cellulose and / or glycine; b) lubricants, e.g., silica, talcum, stearic acid, its magnesium or calcium salt and / or polyethyleneglycol; c) binders, e.g., magnesium aluminum silicate, starch paste, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose and / or polyvinylpyrrolidone; if desired d) disintegrants, e.g., starches, agar, alginic acid or its sodium salt, or effervescent mixtures; and e) absorbents, colorants, flavors and sweeteners.

[0146] In a certain embodiment the pharmaceutical unit dosage form comprises N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide, or a pharmaceutically acceptable salt thereof, mannitol, microcrystalline cellulose, croscarmellose sodium, hydroxypropyl cellulose, colloidal silicon dioxide and magnesium stearate. In an embodiment the pharmaceutical unit dosage form is a hard gelatin capsule. In another embodiment, the pharmaceutical unit dosage form is a hard gelatin capsule, wherein the shell of the hard gelatin capsule comprises gelatin, titanium dioxide, and iron oxide.

[0147] In certain embodiments, the pharmaceutical unit dosage form comprises about 10 mg to about 500 mg of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide suitable, or a pharmaceutically acceptable salt thereof, for oral administration.

[0148] In certain embodiments, the pharmaceutical unit dosage form comprises about 10 mg of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide, or a pharmaceutically acceptable salt thereof, suitable for oral administration.

[0149] In certain embodiments, the pharmaceutical unit dosage form comprises about 20 mg of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide, or a pharmaceutically acceptable salt thereof, suitable for oral administration.

[0150] In certain embodiments, the pharmaceutical unit dosage form comprises about 25 mg of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide, or a pharmaceutically acceptable salt thereof, suitable for oral administration.

[0151] In certain embodiments, the pharmaceutical unit dosage form comprises about 50 mg of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide, or a pharmaceutically acceptable salt thereof, suitable for oral administration.

[0152] In certain embodiments, the pharmaceutical unit dosage form comprises about 100 mg of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2- (4-sulfamoylphenyl)acetamide, or a pharmaceutically acceptable salt thereof, suitable for oral administration.

[0153] In certain embodiments, the pharmaceutical unit dosage form comprises about 200 mg of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2- (4-sulfamoylphenyl)acetamide, or a pharmaceutically acceptable salt thereof, suitable for oral administration.

[0154] In certain embodiments, the pharmaceutical unit dosage form comprises about 400 mg of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2- (4-sulfamoylphenyl)acetamide, or a pharmaceutically acceptable salt thereof, suitable for oral administration.

[0155] In certain embodiments, the pharmaceutical unit dosage form comprises about 10 mg to about 400 mg of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide suitable, or a pharmaceutically acceptable salt thereof, suitable for oral administration of up to a maximum total once a day dose of 400 mg per day of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2- yl)-2-(4-sulfamoylphenyl)acetamide, or a pharmaceutically acceptable salt thereof.

[0156] In certain embodiments, the pharmaceutical unit dosage form comprises about 10 mg to about 200 mg of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide suitable, or a pharmaceutically acceptable salt thereof, suitable for oral administration of up to a maximum total once a day dose of 400 mg per day of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2- yl)-2-(4-sulfamoylphenyl)acetamide, or a pharmaceutically acceptable salt thereof.

[0157] In certain embodiments, the pharmaceutical unit dosage form comprises about 10 mg to about 100 mg of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide suitable, or a pharmaceutically acceptable salt thereof, suitable for oral administration of up to a maximum total once a day dose of 400 mg per day of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2- yl)-2-(4-sulfamoylphenyl)acetamide, or a pharmaceutically acceptable salt thereof.

[0158] In certain embodiments, the pharmaceutical unit dosage form comprises about 10 mg, 20 mg, 25 mg, 50 mg, 100 mg, 200 mg or 400 mg of N-(3-cyano-5-(cyclohexylmethyl)-6,6- dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide suitable, or a pharmaceutically acceptable salt thereof, suitable for oral administration of up to a maximum total once a day dose of 400 mg per day of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-

[0159] 4.5.6.7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide, or a pharmaceutically acceptable salt thereof.

[0160] In certain embodiments, the pharmaceutical unit dosage form comprises about 10 mg, 20 mg, 25 mg, 50 mg, 100 mg, or 200 mg of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-

[0161] 4.5.6.7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide suitable, or a pharmaceutically acceptable salt thereof, suitable for oral administration of up to a maximum total once a day dose of 400 mg per day of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-

[0162] 4.5.6.7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide, or a pharmaceutically acceptable salt thereof.

[0163] In certain embodiments, the pharmaceutical unit dosage form comprises about 10 mg, 20 mg, 25 mg, 50 mg or 100 mg of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide suitable, or a pharmaceutically acceptable salt thereof, suitable for oral administration of up to a maximum total once a day dose of 400 mg per day of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-

[0164] 4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide, or a pharmaceutically acceptable salt thereof.

[0165] In certain embodiments, the pharmaceutical unit dosage form comprises about 100 mg of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2- (4-sulfamoylphenyl)acetamide, or a pharmaceutically acceptable salt thereof, suitable for oral administration of up to a maximum total once a day dose of 400 mg per day of N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide, or a pharmaceutically acceptable salt thereof.

[0166] In certain embodiments, the pharmaceutical unit dosage form comprises about 200 mg of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2- (4-sulfamoylphenyl)acetamide, or a pharmaceutically acceptable salt thereof, suitable for oral administration of up to a maximum total once a day dose of 400 mg per day of N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide, or a pharmaceutically acceptable salt thereof.

[0167] In certain embodiments, the pharmaceutical unit dosage form comprises about 400 mg of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2- (4-sulfamoylphenyl)acetamide, or a pharmaceutically acceptable salt thereof, suitable for oral administration of up to a maximum total once a day dose of 400 mg per day of N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide, or a pharmaceutically acceptable salt thereof.

[0168] In certain embodiments, the pharmaceutical unit dosage form comprises about 50 mg to about 500 mg of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide suitable, or a pharmaceutically acceptable salt thereof, for oral administration.

[0169] In certain embodiments, the pharmaceutical unit dosage form comprises about 50 mg of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide, or a pharmaceutically acceptable salt thereof, suitable for oral administration.

[0170] In certain embodiments, the pharmaceutical unit dosage form comprises about 75 mg of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide, or a pharmaceutically acceptable salt thereof, suitable for oral administration.

[0171] In certain embodiments, the pharmaceutical unit dosage form comprises about 100 mg of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2- (4-sulfamoylphenyl)acetamide, or a pharmaceutically acceptable salt thereof, suitable for oral administration.

[0172] In certain embodiments, the pharmaceutical unit dosage form comprises about 200 mg of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2- (4-sulfamoylphenyl)acetamide, or a pharmaceutically acceptable salt thereof, suitable for oral administration.

[0173] In certain embodiments, the pharmaceutical unit dosage form comprises about 250 mg of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2- (4-sulfamoylphenyl)acetamide, or a pharmaceutically acceptable salt thereof, suitable for oral administration.

[0174] In certain embodiments, the pharmaceutical unit dosage form comprises about 300 mg of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2- (4-sulfamoylphenyl)acetamide, or a pharmaceutically acceptable salt thereof, suitable for oral administration.

[0175] In certain embodiments, the pharmaceutical unit dosage form comprises about 400 mg of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2- (4-sulfamoylphenyl)acetamide, or a pharmaceutically acceptable salt thereof, suitable for oral administration.

[0176] In certain embodiments, the pharmaceutical unit dosage form comprises about 500 mg of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2- (4-sulfamoylphenyl)acetamide, or a pharmaceutically acceptable salt thereof, suitable for oral administration.

[0177] In certain embodiments, the pharmaceutical unit dosage form comprises about 50 mg to about 500 mg of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide suitable, or a pharmaceutically acceptable salt thereof, suitable for oral administration of up to a maximum total twice a day dose of 500 mg per day of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2- yl)-2-(4-sulfamoylphenyl)acetamide, or a pharmaceutically acceptable salt thereof.

[0178] In certain embodiments, the pharmaceutical unit dosage form comprises about 50 mg to about 250 mg of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide suitable, or a pharmaceutically acceptable salt thereof, suitable for oral administration of up to a maximum total twice a day dose of 500 mg per day of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2- yl)-2-(4-sulfamoylphenyl)acetamide, or a pharmaceutically acceptable salt thereof.

[0179] In certain embodiments, the pharmaceutical unit dosage form comprises about 50 mg to about 100 mg of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide suitable, or a pharmaceutically acceptable salt thereof, suitable for oral administration of up to a maximum total twice a day dose of 500 mg per day of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2- yl)-2-(4-sulfamoylphenyl)acetamide, or a pharmaceutically acceptable salt thereof.

[0180] In certain embodiments, the pharmaceutical unit dosage form comprises about 50 mg, 75 mg, 100 mg, 200 mg, 250 mg or 500 mg, of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl- 4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide suitable, or a pharmaceutically acceptable salt thereof, suitable for oral administration of up to a maximum total twice a day dose of 500 mg per day of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl- 4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide, or a pharmaceutically acceptable salt thereof.

[0181] In certain embodiments, the pharmaceutical unit dosage form comprises about 50 mg, 75 mg, 100 mg, 200 mg or 250 mg of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide suitable, or a pharmaceutically acceptable salt thereof, suitable for oral administration of up to a maximum total twice a day dose of 500 mg per day of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl- 4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide, or a pharmaceutically acceptable salt thereof.

[0182] In certain embodiments, the pharmaceutical unit dosage form comprises about 50 mg, 75 mg or 100 mg of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide suitable, or a pharmaceutically acceptable salt thereof, suitable for oral administration of up to a maximum total twice a day dose of 500 mg per day of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2- yl)-2-(4-sulfamoylphenyl)acetamide, or a pharmaceutically acceptable salt thereof.

[0183] In certain embodiments, the pharmaceutical unit dosage form comprises about 100 mg of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2- (4-sulfamoylphenyl)acetamide, or a pharmaceutically acceptable salt thereof, suitable for oral administration of up to a maximum total twice a day dose of 500 mg per day of N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide, or a pharmaceutically acceptable salt thereof.

[0184] In certain embodiments, the pharmaceutical unit dosage form comprises about 10 mg to about 100 mg of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide suitable for oral administration of up to a maximum total twice a day dose of 1000 mg per day of N-(3-cyano-5-(cyclohexylmethyl)-6,6- dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide.

[0185] In certain embodiments, the pharmaceutical unit dosage form comprises about 100 mg of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2- (4-sulfamoylphenyl)acetamide suitable for oral administration of up to a maximum total twice a day dose of 1000 mg per day of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide.

[0186] In certain embodiments of the above pharmaceutical compositions or pharmaceutical unit dosage forms the N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is present as a N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide mesylate salt.

[0187] In certain embodiments of the above pharmaceutical compositions or pharmaceutical unit dosage forms the N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is present as a N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide gentisate salt.

[0188] In certain embodiments of the above pharmaceutical compositions or pharmaceutical unit dosage forms the N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is present as a N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide free base.

[0189] The aforementioned pharmaceutical compositions or pharmaceutical unit dosage forms are orally administered for the treatment or prevention of a dengue virus disease or disorder. In certain embodiments the pharmaceutical unit dosage forms are orally administered for the treatment or prevention of a dengue virus disease or disorder, wherein the disease or disorder is dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). In certain embodiments the pharmaceutical unit dosage forms are orally administered for the treatment or prevention of a dengue virus disease or disorder, wherein the disease or disorder is dengue hemorrhagic fever (DHF).

[0190] In another aspect, the present invention provides the use of N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for the treatment or prevention of a dengue virus disease or disorder, wherein N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is present in an amount of about 10 mg to about 500 mg. In certain embodiments the disease or disorder is dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). In certain embodiments the disease or disorder is dengue hemorrhagic fever (DHF).

[0191] In an embodiment, the present invention provides the use of N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for the treatment or prevention of a dengue virus disease or disorder, wherein N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is present in an amount of about 10 mg to about 250 mg. In certain embodiments the disease or disorder is dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). In certain embodiments the disease or disorder is dengue hemorrhagic fever (DHF).

[0192] In another embodiment, the present invention provides the use of N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for the treatment or prevention of a dengue virus disease or disorder, wherein N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is present in an amount of about 10 mg to about 100 mg. In certain embodiments the disease or disorder is dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). In certain embodiments the disease or disorder is dengue hemorrhagic fever (DHF).

[0193] In another aspect, the present invention provides the use of N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for the treatment or prevention of a dengue virus disease or disorder, wherein N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is present in an amount of about 100 mg. In certain embodiments the disease or disorder is dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). In certain embodiments the disease or disorder is dengue hemorrhagic fever (DHF).

[0194] In certain embodiments of the above use of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-

[0195] 4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament, the N-(3- cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is present as a N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide mesylate salt.

[0196] In certain embodiments of the above use of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-

[0197] 4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament, the N-(3- cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is present as a N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide gentisate salt.

[0198] In certain embodiments of the above use of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-

[0199] 4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament, the N-(3- cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is present as a N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide free base. In certain embodiments, of the invention is a medicament comprising N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, wherein Compound (1), or a pharmaceutically acceptable salt thereof, is present in an amount of about 10 mg to about 400 mg.

[0200] In certain embodiments, of the invention is a medicament comprising N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, wherein Compound (1), or a pharmaceutically acceptable salt thereof, is present in an amount of about 10 mg to about 200 mg.

[0201] In certain embodiments, of the invention is a medicament comprising N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, wherein Compound (1), or a pharmaceutically acceptable salt thereof, is present in an amount of about 10 mg to about 100 mg.

[0202] In certain embodiments, of the invention is a medicament comprising N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, wherein Compound (1), or a pharmaceutically acceptable salt thereof, is present in an amount of about 10 mg, 20 mg, 25 mg, 50 mg, 100 mg, 200 mg or 400 mg.

[0203] In certain embodiments, of the invention is a medicament comprising N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, wherein Compound (1), or a pharmaceutically acceptable salt thereof, is present in an amount of about 10 mg, 20 mg, 25 mg, 50 mg, 100 mg, or 200 mg.

[0204] In certain embodiments, of the invention is a medicament comprising N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, wherein Compound (1), or a pharmaceutically acceptable salt thereof, is present in an amount of about 10 mg, 20 mg, 25 mg, 50 mg or 100 mg.

[0205] In certain embodiments, of the invention is a medicament comprising N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, wherein Compound (1), or a pharmaceutically acceptable salt thereof, is present in an amount of about 50 mg to about 500 mg.

[0206] In certain embodiments, of the invention is a medicament comprising N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, wherein Compound (1), or a pharmaceutically acceptable salt thereof, is present in an amount of about 50 mg to about 250 mg.

[0207] In certain embodiments, of the invention is a medicament comprising N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, wherein Compound (1), or a pharmaceutically acceptable salt thereof, is present in an amount of about 50 mg to about 100 mg.

[0208] In certain embodiments, of the invention is a medicament comprising N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, wherein Compound (1), or a pharmaceutically acceptable salt thereof, is present in an amount of about 50 mg, 75 mg, 100 mg, 200 mg, 250 mg or 500 mg.

[0209] In certain embodiments, of the invention is a medicament comprising N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, wherein Compound (1), or a pharmaceutically acceptable salt thereof, is present in an amount of about 50 mg, 75 mg, 100 mg, 200 mg or 250 mg.

[0210] In certain embodiments, of the invention is a medicament comprising N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, wherein Compound (1), or a pharmaceutically acceptable salt thereof, is present in an amount of about 50 mg, 75 mg or 100 mg.

[0211] In certain embodiments, of the invention is a medicament comprising N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, wherein Compound (1), or a pharmaceutically acceptable salt thereof, is present in an amount of about 50 mg.

[0212] In certain embodiments, of the invention is a medicament comprising N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, wherein Compound (1), or a pharmaceutically acceptable salt thereof, is present in an amount of about 75 mg.

[0213] In certain embodiments, of the invention is a medicament comprising N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, wherein Compound (1), or a pharmaceutically acceptable salt thereof, is present in an amount of about 100 mg.

[0214] In certain embodiments, of the invention is a medicament comprising N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, wherein Compound (1), or a pharmaceutically acceptable salt thereof, is present in an amount of about 200 mg.

[0215] In certain embodiments, of the invention is a medicament comprising N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, wherein Compound (1), or a pharmaceutically acceptable salt thereof, is present in an amount of about 250 mg.

[0216] In certain embodiments, of the invention is a medicament comprising N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, wherein Compound (1), or a pharmaceutically acceptable salt thereof, is present in an amount of about 300 mg.

[0217] In certain embodiments, of the invention is a medicament comprising N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, wherein Compound (1), or a pharmaceutically acceptable salt thereof, is present in an amount of about 400 mg.

[0218] In certain embodiments, of the invention is a medicament comprising N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, wherein Compound (1), or a pharmaceutically acceptable salt thereof, is present in an amount of about 500 mg. In certain embodiments, of the invention is a medicament comprising N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, wherein Compound (1), or a pharmaceutically acceptable salt thereof, is present in an amount of about 50 mg to about 250 mg.

[0219] In certain embodiments, of the invention is a medicament comprising N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, wherein Compound (1), or a pharmaceutically acceptable salt thereof, is present in an amount of about 50 mg to about 100 mg.

[0220] In certain embodiments, of the invention is a medicament comprising N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, wherein Compound (1), or a pharmaceutically acceptable salt thereof, is present in an amount of about 50 mg, 75 mg, 100 mg, 200 mg, 250 mg or 500 mg.

[0221] In certain embodiments, of the invention is a medicament comprising N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, wherein Compound (1), or a pharmaceutically acceptable salt thereof, is present in an amount of about 50 mg, 75 mg, 100 mg, 200 mg or 250 mg.

[0222] In certain embodiments, of the invention is a medicament comprising N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, wherein Compound (1), or a pharmaceutically acceptable salt thereof, is present in an amount of about 50 mg, 75 mg or 100 mg.

[0223] In certain embodiments of the above medicaments the N-(3-cyano-5-(cyclohexylmethyl)- 6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is present as a N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide mesylate salt.

[0224] In certain embodiments of the above medicaments the N-(3-cyano-5-(cyclohexylmethyl)- 6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is present as a N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide gentisate salt.

[0225] In certain embodiments of the above medicaments the N-(3-cyano-5-(cyclohexylmethyl)- 6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is present as a N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide free base.

[0226] In certain embodiments of the above medicaments the disease or disorder is dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). In certain embodiments the disease or disorder is dengue hemorrhagic fever (DHF).

[0227] In another aspect, the present invention provides a medicament comprising N-(3-cyano- 5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide, or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, wherein N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is present in an amount of about 10 mg to about 100 mg. In certain embodiments the disease or disorder is dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). In certain embodiments the disease or disorder is dengue hemorrhagic fever (DHF).

[0228] In another aspect, the present invention provides a medicament comprising N-(3-cyano- 5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide, or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, wherein N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is present in an amount of about 100 mg. In certain the disease or disorder is dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). In certain embodiments the disease or disorder is dengue hemorrhagic fever (DHF).

[0229] Pharmacology and Utility

[0230] In another aspect, the present invention provides the use of the dosages, dosage forms, medicaments, pharmaceutical compositions and dosage regimens provided herein in the treatment or prevention of a dengue virus disease or disorder. In certain embodiments the dengue virus disease or disorder is dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). In certain embodiments the dengue virus disease or disorder is dengue hemorrhagic fever (DHF).

[0231] Accordingly, the invention further provides a method for treating or preventing a dengue virus disease or disorder in a subject in need thereof using the dosages, dosage forms, medicaments, pharmaceutical compositions, and dosage regimens provided herein.

[0232] An aspect of the invention is a method for treating or preventing a dengue virus disease or disorder in a subject in need thereof, comprising orally administering a therapeutically effective amount of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin- 2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, to the subject, wherein N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day, or N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyljacetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day.

[0233] In an embodiment of the method of treating or preventing a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2- yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day at a dose of about 10 mg to about 400 mg, or N-(3- cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyljacetamide (Compound (1), or a pharmaceutically acceptable salt thereof,), is orally administered twice a day where each dose is about 300 mg to about 500 mg.

[0234] In an embodiment of the method of treating or preventing a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2- yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day.

[0235] In a certain embodiment of the once a day treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day at a dose of about 10 mg to about 400 mg.

[0236] In a certain embodiment of the once a day treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day at a dose of about 10 mg, about 30 mg, about 50 mg, about 100 mg, about 150 mg, about 300 mg, or about 400 mg.

[0237] In a certain embodiment of the once a day treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day at a dose of about 300 mg, or about 400 mg.

[0238] In a certain embodiment of the once a day treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day at a dose of about 400 mg.

[0239] In a certain embodiment of the once a day treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day at a dose of 400 mg.

[0240] In an embodiment of the once a day method of treating or preventing a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days.

[0241] In an embodiment of the once a day treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2- yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day for 5 days.

[0242] In a certain embodiment of the once a day treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days at a dose of about 10 mg to about 400 mg.

[0243] In a certain embodiment of the once a day treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day for 5 days at a dose of about 10 mg to about 400 mg.

[0244] In a certain embodiment of the once a day treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days at a dose of about 10 mg, about 30 mg, about 50 mg, about 100 mg, about 150 mg, about 300 mg, or about 400 mg.

[0245] In a certain embodiment of the once a day treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day for 5 days at a dose of about 10 mg, about 30 mg, about 50 mg, about 100 mg, about 150 mg, about 300 mg, or about 400 mg.

[0246] In a certain embodiment of the once a day treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days at a dose of about 300 mg, or about 400 mg.

[0247] In a certain embodiment of the once a day treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day for 5 days at a dose of about 300 mg, or about 400 mg.

[0248] In a certain embodiment of the once a day treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days at a dose of about 400 mg.

[0249] In a certain embodiment N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day for 5 days at a dose of about 400 mg.

[0250] In a certain embodiment of the once a day treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days at a dose of 400 mg.

[0251] In a certain embodiment N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day for 5 days at a dose of 400 mg.

[0252] In a certain embodiment of the once a day treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day for 5 days at a dose of 400 mg.

[0253] In an embodiment of the method of treating or preventing a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2- yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day.

[0254] In a certain embodiment of the twice a day treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day where each dose is about 300 mg to about 500 mg.

[0255] In a certain embodiment of the twice a day treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day where each dose is about 300 mg, about 400 mg or about 500 mg.

[0256] In a certain embodiment of the twice a day treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day where each dose is about 400 mg or about 500 mg.

[0257] In a certain embodiment of the twice a day treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day where each dose is about 400 mg.

[0258] In a certain embodiment of the twice a day treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day where each dose is about 500 mg.

[0259] In a certain embodiment of the twice a day treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day where each dose is 500 mg.

[0260] In an embodiment of the twice a day method of treating or preventing a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days.

[0261] In an embodiment of the twice a day treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2- yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 1 day.

[0262] In an embodiment of the twice a day treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2- yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 2 days.

[0263] In an embodiment of the twice a day treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2- yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 3 days.

[0264] In an embodiment of the twice a day treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2- yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 4 days.

[0265] In an embodiment of the twice a day treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2- yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 5 days.

[0266] In an embodiment of the twice a day treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2- yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 6 days.

[0267] In an embodiment of the twice a day treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2- yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 7 days.

[0268] In a certain embodiment of the twice a day treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days, where each dose is about 300 mg to about 500 mg.

[0269] In a certain embodiment of the twice a day treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 5 days, where each dose is about 300 mg to about 500 mg.

[0270] In a certain embodiment of the twice a day treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days, where each dose is about 300 mg, about 400 mg, or about 500 mg.

[0271] In a certain embodiment of the twice a day treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 5 days, where each dose is about 300 mg, about 400 mg, or about 500 mg.

[0272] In a certain embodiment of the twice a day treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days, where each dose is about 400 mg, or about 500 mg.

[0273] In a certain embodiment of the twice a day treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 5 days, where each dose is about 400 mg, or about 500 mg.

[0274] In a certain embodiment of the twice a day treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days, where each dose is about 400 mg.

[0275] In a certain embodiment of the twice a day treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 5 days, where each dose is about 400 mg.

[0276] In a certain embodiment of the twice a day treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days, where each dose is about 500 mg.

[0277] In a certain embodiment of the twice a day treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 5 days, where each dose is about 500 mg.

[0278] In a certain embodiment of the twice a day treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days, where each dose is 500 mg.

[0279] In a certain embodiment of the twice a day treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 5 days, where each dose is 500 mg.

[0280] In certain embodiments of the above methods of treatment or prevention of a dengue virus disease or disorder, the N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered as a N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide mesylate salt.

[0281] In certain embodiments of the above methods of treatment or prevention of a dengue virus disease or disorder, the N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered as a N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide gentisate salt.

[0282] In certain embodiments of the above methods of treatment or prevention of a dengue virus disease or disorder, the N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered as a N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide free base.

[0283] In certain embodiments of the above methods of treatment or prevention of a dengue virus disease or disorder, the dengue virus disease or disorder is dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). In certain embodiments the dengue virus disease or disorder is dengue hemorrhagic fever (DHF).

[0284] The invention further provides the use of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl- 4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the treatment or prevention of a dengue virus disease or disorder, wherein N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is administered once a day, or N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is administered twice a day.

[0285] In an embodiment of the use of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day at a dose of about 10 mg to about 400 mg, or N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2- yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day where each dose is about 300 mg to about 500 mg.

[0286] In an embodiment of the use of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day.

[0287] In a certain embodiment of the use of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day at a dose of about 10 mg to about 400 mg.

[0288] In a certain embodiment of the use of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day at a dose of about 10 mg, about 30 mg, about 50 mg, about 100 mg, about 150 mg, about 300 mg, or about 400 mg.

[0289] In a certain embodiment of the use of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day at a dose of about 300 mg, or about 400 mg.

[0290] In a certain embodiment of the use of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day at a dose of about 400 mg. In a certain embodiment of the use of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day at a dose of 400 mg.

[0291] In an embodiment of the use of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days.

[0292] In an embodiment of the use of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day for 5 days.

[0293] In a certain embodiment of the use of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days at a dose of about 10 mg to about 400 mg.

[0294] In a certain embodiment of the use of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day for 5 days at a dose of about 10 mg to about 400 mg.

[0295] In a certain embodiment of the use of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days at a dose of about 10 mg, about 30 mg, about 50 mg, about 100 mg, about 150 mg, about 300 mg, or about 400 mg.

[0296] In a certain embodiment of the use of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day for 5 days at a dose of about 10 mg, about 30 mg, about 50 mg, about 100 mg, about 150 mg, about 300 mg, or about 400 mg.

[0297] In a certain embodiment of the use of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days at a dose of about 300 mg, or about 400 mg.

[0298] In a certain embodiment of the use of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day for 5 days at a dose of about 300 mg, or about 400 mg.

[0299] In a certain embodiment of the use of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days at a dose of about 400 mg.

[0300] In a certain embodiment of the use of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day for 5 days at a dose of about 400 mg.

[0301] In a certain embodiment of the use of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days at a dose of 400 mg.

[0302] In a certain embodiment of the use of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day for 5 days at a dose of 400 mg.

[0303] In an embodiment of the use of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day.

[0304] In a certain embodiment of the use of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day where each dose is about 300 mg to about 500 mg.

[0305] In a certain embodiment of the use of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day where each dose is about 300 mg, about 400 mg or about 500 mg.

[0306] In a certain embodiment of the use of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day where each dose is about 400 mg or about 500 mg.

[0307] In a certain embodiment of the use of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day where each dose is about 400 mg. In a certain embodiment N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day where each dose is about 500 mg.

[0308] In a certain embodiment of the use of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day where each dose is about 400 mg. In a certain embodiment N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day where each dose is 500 mg.

[0309] In an embodiment of the use of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days.

[0310] In an embodiment of the use of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 5 days.

[0311] In a certain embodiment of the use of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days, where each dose is about 300 mg to about 500 mg.

[0312] In a certain embodiment of the use of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 5 days, where each dose is about 300 mg to about 500 mg.

[0313] In a certain embodiment of the use of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days, where each dose is about 300 mg, about 400 mg, or about 500 mg.

[0314] In a certain embodiment of the use of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 5 days, where each dose is about 300 mg, about 400 mg, or about 500 mg.

[0315] In a certain embodiment of the use of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days, where each dose is about 400 mg, or about 500 mg.

[0316] In a certain embodiment of the use of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 5 days, where each dose is about 400 mg, or about 500 mg. In a certain embodiment of the use of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days, where each dose is about 400 mg. In a certain embodiment N-(3- cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 5 days, where each dose is about 400 mg.

[0317] In a certain embodiment of the use of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days, where each dose is about 500 mg.

[0318] In a certain embodiment of the use of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 5 days, where each dose is about 500 mg.

[0319] In a certain embodiment of the use of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days, where each dose is 500 mg.

[0320] In a certain embodiment of the use of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 5 days, where each dose is 500 mg. In certain embodiments of the use of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the treatment or prevention of a dengue virus disease or disorder, the N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered as a N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide mesylate salt.

[0321] In certain embodiments of the use of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the treatment or prevention of a dengue virus disease or disorder, the N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered as a N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide gentisate salt.

[0322] In certain embodiments of the use of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the treatment or prevention of a dengue virus disease or disorder, the N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered as a N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide free base.

[0323] In certain embodiments of the above use of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl- 4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, in the treatment or prevention of a dengue virus disease or disorder, the dengue virus disease or disorder is dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). In certain embodiments the dengue virus disease or disorder is dengue hemorrhagic fever (DHF).

[0324] The invention further provides N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, wherein N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is administered once a day, or N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is administered twice a day.

[0325] In an embodiment of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day at a dose of about 10 mg to about 400 mg, or N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1), or a pharmaceutically acceptable salt thereof,), is orally administered twice a day where each dose is about 300 mg to about 500 mg.

[0326] In an embodiment of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day.

[0327] In a certain embodiment of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day at a dose of about 10 mg to about 400 mg.

[0328] In a certain embodiment of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day at a dose of about 10 mg, about 30 mg, about 50 mg, about 100 mg, about 150 mg, about 300 mg, or about 400 mg.

[0329] In a certain embodiment of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day at a dose of about 300 mg, or about 400 mg.

[0330] In a certain embodiment of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day at a dose of about 400 mg.

[0331] In a certain embodiment of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day at a dose of 400 mg.

[0332] In an embodiment of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days.

[0333] In an embodiment of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day for 5 days.

[0334] In a certain embodiment of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days at a dose of about 10 mg to about 400 mg.

[0335] In a certain embodiment of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day for 5 days at a dose of about 10 mg to about 400 mg.

[0336] In a certain embodiment of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days at a dose of about 10 mg, about 30 mg, about 50 mg, about 100 mg, about 150 mg, about 300 mg, or about 400 mg.

[0337] In a certain embodiment of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day for 5 days at a dose of about 10 mg, about 30 mg, about 50 mg, about 100 mg, about 150 mg, about 300 mg, or about 400 mg.

[0338] In a certain embodiment of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days at a dose of about 300 mg, or about 400 mg.

[0339] In a certain embodiment of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day for 5 days at a dose of about 300 mg, or about 400 mg.

[0340] In a certain embodiment of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days at a dose of about 400 mg.

[0341] In a certain of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, embodiment N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day for 5 days at a dose of about 400 mg.

[0342] In a certain embodiment of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days at a dose of 400 mg.

[0343] In a certain of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, embodiment N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day for 5 days at a dose of 400 mg.

[0344] In an embodiment of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day.

[0345] In a certain embodiment of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day where each dose is about 300 mg to about 500 mg.

[0346] In a certain embodiment of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day where each dose is about 300 mg, about 400 mg or about 500 mg.

[0347] In a certain embodiment of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day where each dose is about 400 mg or about 500 mg.

[0348] In a certain embodiment of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day where each dose is about 400 mg.

[0349] In a certain embodiment of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day where each dose is about 500 mg.

[0350] In an embodiment of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days.

[0351] In an embodiment of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 5 days.

[0352] In a certain embodiment of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days, where each dose is about 300 mg to about 500 mg.

[0353] In a certain embodiment of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 5 days, where each dose is about 300 mg to about 500 mg.

[0354] In a certain embodiment of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days, where each dose is about 300 mg, about 400 mg, or about 500 mg.

[0355] In a certain embodiment of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 5 days, where each dose is about 300 mg, about 400 mg, or about 500 mg.

[0356] In a certain embodiment of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days, where each dose is about 400 mg, or about 500 mg.

[0357] In a certain embodiment of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 5 days, where each dose is about 400 mg, or about 500 mg.

[0358] In a certain embodiment of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days, where each dose is about 400 mg.

[0359] In a certain embodiment of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 5 days, where each dose is about 400 mg.

[0360] In a certain embodiment of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days, where each dose is about 500 mg.

[0361] In a certain embodiment of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 5 days, where each dose is about 500 mg.

[0362] In a certain embodiment of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days, where each dose is 500 mg.

[0363] In a certain embodiment of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 5 days, where each dose is 500 mg.

[0364] In certain embodiments of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, the N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered as a N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide mesylate salt.

[0365] In certain embodiments of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, the N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered as a N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide gentisate salt.

[0366] In certain embodiments of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, the N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered as a N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide free base.

[0367] In certain embodiments of N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of a dengue virus disease or disorder, the dengue virus disease or disorder is dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). In certain embodiments the dengue virus disease or disorder is dengue hemorrhagic fever (DHF).

[0368] EXAMPLES

[0369] Example 1: A first-in human, randomized, participant and investigator blinded, placebo controlled, single and multiple ascending dose study to assess the safety, tolerability, and pharmacokinetics of EYU688 in healthy subjects.

[0370] Following administration of single (10 - 400 mg) or multiple dosing (30-300 mg, QD for 5 days and 300-500mg BID for 5 days), the pharmacokinetic data showed variability across cohorts, especially for Cmax and AUG exposures (CV up to 100%). N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (EYLI688) exposure in blood and plasma increased generally in a dose-proportional manner over the dose range examined in both SAD and MAD cohorts. EYLI688 is rapidly absorbed with a median Tmax of 1 .0 to 2 hours post dose in blood and plasma across dose levels. Following multiple oral dose administration, the mean terminal half-life for EYLI688 ranged from 12.5 to 17.9 hours in blood and 10.1 to 16.0 hours in plasma on Day 5, comparable to that observed in the SAD arms. Following multiple dosing of EYLI688 (30 mg QD to 500 mg BID for 5 days), the accumulation ratio was observed between 0.99 to 2.05-fold in blood and 1.75 to 4.67-fold in plasma on day 5 compared to day 1. Following a single oral administration of EYLI688 at 10 to 400 mg dose levels, less than 0.4% of the dose was excreted in urine. The blood to plasma partitioning ratio was considered above 1 for all cohorts, indicating distribution of EYLI688 into red blood cells. Following 5 days of 500 mg BID dosing (9 doses), the mean plasma Cmax on day 5 was 2580 ng / ml and the mean plasma ALICtau was 17320 hr*ng / mL.

[0371] A total of 88 healthy volunteers had received EYLI688 or matching placebo with 66 healthy volunteers exposed to EYLI688. The dose range for a single dose was from 10mg to 400mg, and from 30 mg to 300 mg QD and from 300 mg to 500 mg BID for a duration of 5 days. Overall, the adverse events observed were Common Terminology criteria for adverse events (CTCAE) Grade 1 to 2. No serious adverse events have been reported.

[0372] The safety data suggest that EYLI688 is safe and well tolerated at all doses tested (up to 400 mg single dose and 500 mg BID multiple dose (9 doses)).

Claims

CLAIMS:

1. A method for treating or preventing a dengue virus disease or disorder in a subject in need thereof, comprising orally administering a therapeutically effective amount of N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, to the subject,Compound (1) wherein N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2- c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered once a day, or N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day.

2. The method of claim 1 , wherein N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days.

3. The method of claim 2, wherein N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 5 days.

4. The method of claim 3, wherein N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 5 days where each dose is about 300 mg to about 500 mg.

5. The method of claim 4, wherein N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 5 days where each dose is about 300 mg, about 400 mg or about 500 mg.

6. The method of claim 5, wherein N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 5 days where each dose is about 500 mg.

7. The method of claim 6, wherein N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 5 days where each dose is 500 mg.

8. The method of any one of claims 1 to 7, wherein the N-(3-cyano-5-(cyclohexylmethyl)-6,6- dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered as a N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2- (4-sulfamoylphenyl)acetamide mesylate salt.

9. The method of any one of claims 1 to 7, wherein the N-(3-cyano-5-(cyclohexylmethyl)-6,6- dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered as a N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2- (4-sulfamoylphenyl)acetamide gentisate salt.

10. The method of any one of claims 1 to 7, wherein the N-(3-cyano-5-(cyclohexylmethyl)-6,6- dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered as a N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2- (4-sulfamoylphenyl)acetamide free base.

11. The method of any one of claims 1 to 10, wherein the dengue virus disease or disorder is dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS).

12. The method of any one of claims 1 to 11 , wherein the dengue virus disease or disorder is dengue hemorrhagic fever (DHF).

13. A dosing regimen for treating or preventing a dengue virus disease or disorder, wherein the regimen comprises orally administering N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl- 4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, once a day, or the regimen comprises orally administering N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1), or a pharmaceutically acceptable salt thereof, twice a dayCompound (1).

14. The dosing regimen of claim 13, wherein N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days.

15. The dosing regimen of claim 14, wherein N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 5 days.

16. The dosing regimen of claim 15, wherein N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 5 days where each dose is about 300 mg to about 500 mg.

17. The dosing regimen of claim 16, wherein N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 5 days where each dose is about 300 mg, about 400 mg or about 500 mg.

18. The dosing regimen of claim 17, wherein N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 5 days where each dose is about 500 mg.

19. The dosing regimen of claim 18, wherein N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered twice a day for 5 days where each dose is 500 mg.

20. The dosing regimen of any one of claims 13 to 19, wherein the N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered as a N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide mesylate salt.

21. The dosing regimen of any one of claims 13 to 19, wherein the N-(3-cyano-5- (cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered as a N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide gentisate salt.

22. The dosing regimen of any one of claims 13 to 19, wherein the N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4- sulfamoylphenyl)acetamide (Compound (1)), or a pharmaceutically acceptable salt thereof, is orally administered as a N-(3-cyano-5-(cyclohexylmethyl)-6,6-dimethyl-4, 5,6,7- tetrahydrothieno[3,2-c]pyridin-2-yl)-2-(4-sulfamoylphenyl)acetamide free base.

23. The dosing regimen of any one of claims 13 to 22, wherein the dengue virus disease or disorder is dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS).

24. The dosing regimen of any one of claims 13 to 23, wherein the dengue virus disease or disorder is dengue hemorrhagic fever (DHF).

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